Regulation of vascular endothelial growth factor expression in human coloncancer by interleukin-1 beta

Expression of vascular endothelial growth factor (VEGF), an important angio genic factor in colon cancer, is tightly regulated by factors in the microe nvironment. However, specific factors indigenous to the organ microenvironm ent of colon cancer growth that regulate VEGF expression in human colon can cer are not well defined. We investigated interleukin-1 beta (IL-1 beta) in duction of VEGF expression in colon cancer cells and the mechanism by which this occurs. HT29 human colon cancer cells were treated with IL-1 beta for various periods. Induction of VEGF mRNA by IL-1 beta peaked at 24 h (> fiv efold) and returned to baseline by 48 h. SW620 human colon cancer cells als o reached a peak induction of VEGF mRNA 24 h after treatment with IL-1 beta . VEGF was induced at a dose range between 1 and 20 ng ml(-1) of IL-1 beta. IL-1 beta induction of VEGF was also confirmed at the protein level. To ex amine the mechanism for VEGF induction by IL-1 beta, we transiently transfe cted VEGF promoter-reporter constructs into HT29 cells. IL-1 beta increased the activity of the VEGF promoter-reporter construct. Pretreatment of HT29 cells with dactinomycin abrogated the induction of VEGF mRNA by IL-1 beta. The half-life of VEGF mRNA was not prolonged by treatment with IL-1 beta. These findings suggest that IL-1 beta regulates VEGF expression in human co lon cancer cells by increasing transcription of the VEGF gene.